MX2008014536A - Cellular regenerator compound. - Google Patents

Abstract

Described is a process for the manufacture and application of a Cellular Regenerator Compound (CRC), which is locally, intramuscularly or intravenously applied, the same being useful for releasing pluripotential stem cells into the blood circulation of patients suffering from diverse chronic and degenerative disorders, wherein chronic renal insufficiency is included as well as diabetes mellitus, neurodegenerative disorders and anti-age. The formula of the CRC compound allows cryopreserved pluripotential stem cells to be parenterally, locally or topically applied, which do not generate tumours, or cause genetic modifications or alterations; the cells are cryopreserved or lyophilized in culture cell line vessels or Petri dishes, which after being gradually defrosted from 20°C to 8°C are pre-hydrated with a first base solution of the cellular regeneration compound (vessel A). The Cellular Regeneration Compound (CRC) is sequentially prepared based on five solutions A, B, C and D, the purp ose of the present invention is to describe the form of preparation of the four base solutions integrating the CRC which is an invention that is not currently available on the market, which facilitates the application of stem cells by parenteral injections or topical application in order to avoid HLA gene typification studies, surgical interventions as well as interventionist radiology procedures commonly used in stem cell implants or transplants. The cellular regeneration compound (A, B, C and D vessels) acts as a vehicle for the release of suitable and safe amounts of stem cells in cell therapy, regenerative medicine and anti-aging protocols; the compound has been previously used and has shown to be useful for the treatment of a plurality of chronic and degenerative diseases, which do not have conventional treatments for reversing the progression thereof and require cells to be regenerated such as: chronic renal insufficiency, diabetes mellitus, arthrosis, Parkinson¿s disease, viti ligo, etc, for which a minimum of 5 to 10 intravenous injections of 6 ml of CRC are to be applied minimum every seven days.

Description

"COMPOSITE OF CELLULAR REGENERATION" BACKGROUND OF THE INVENTION The stem cells known in English as stem cells, are also known as "stem cells", "trunk cells", "precursor cells", "progenitor cells" and "stem cells". Stem cells are the precursors of approximately more than two hundred strains of differentiated cells that make up the human body.

Stem cells have the ability to go through different stages of maturation or partial differentiation processes and as they get closer to the morphology of the specific tissue, they lose the pluripotential capacity; which is at its maximum expression, when they are in their initial differentiation state, as they are committed to a certain cell lineage they acquire specialized capacity and functions that make them to be specific cells and are those that make up the specialized tissues , as are the neurons in the nervous system, the insulin-producing beta cells in the endocrine tissue of the pancreas, the cardiomyocytes in the myocardium, the cartilage condors that subsequently give rise to the bone tissue, etc.

Stem cells are characterized by the fact that they can be divided simultaneously to maintain a cellular self-renewal; that is, a sustained production of stem cells similar to it, by transdifferentiation and tropism, which allows them to generate daughter cells committed to a specific cell line, in addition to having the ability to migrate to the site of injury or damage in which it occurs cell differentiation, after implantation occurs, being able to observe the phenomenon of cellular regeneration in healthy and diseased tissues (Sánchez-González DJ, Trejo-Bahena, NI Cellular and Molecular Biology, Editorial Alfil, Mexico City, 2006). These characteristics make plausible the injection of stem cells as a potential therapeutic, useful to carry out cell regeneration in patients. (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Cellular Therapy with Stem Cells and Regenerated Medicine, Editorial Alfil, México Distrito Federal, 2008).

Thomson et al (U.S. Patent No. 5, 843, 780, Proc. Nati, Acad. Sci. USA 92: 7844, 1995) were the first to isolate and propagate primate stem cells. Subsequently, they derived the first cell line of human stem cells from the blastocysts. Gearhart and co-workers derived germ-stem cells from fetal tissues of gonadal origin (Shamblott et al Proc Nati, Acad Sci USA 95: 13726, 1998 and U.S. Patent No. 6,090,622). Both stem cells derived from blastocysts and those obtained from gonadal tissues have characteristics that define them as pluripotentencial stem cells, that is to say; are those stem cells that can be grown for long periods of time, without these cells entering the process of differentiation, maintaining a normal morphology and karyotyping (never neoplastic), being able to differentiate into a significant number of specialized cells, such as endothelium, neurons, blood cells, etc. The most important problem in using pluripotentiary stem cells in therapy protocols is that these stem cells are traditionally cultured on a bed of cells (feeder cells) that prevent differentiation (US Pat. No. 5, 843, 780, US Pat. No. 6, 090,622). According to the experiments of Thomson et al. (Science 282: 114, 1998), when stem cells are grown without a bed of cells (feeder cells), the stem cells die and begin to differentiate in a disordered manner.

In the International patent published by Geron Corp. (WO 99/20741), entitled: "Methods and materials for the growth of stem cells derived from primordial primate cells", a cell culture medium for growing stem cells of primates and that they remain in a state of undifferentiation under conditions of low osmotic pressure and low levels of endotoxins.This cell culture medium can combine serum to support the stem cells and the cell bed, the cell culture medium further includes non-essential amino acids, antioxidants, nucleotide growth factors and pyruvate salts. Another International patent published by Geron Corp. (WO 01/51616) entitled: "Techniques of growth and differentiation of pluripotent human stem cells".

DESCRIPTION OF THE INVENTION Based on the review of the state of the art written in the background of this application, it can be seen that the therapies based on stem cells have been carried out directly and using fresh cells from bone marrow, umbilical cord or stem cell cell lines Cultured and purified pluripotentials, which are implanted at the site of damage or through bone marrow transplants (similar to blood transfusion), therapeutic procedures that necessarily include the gene typing of the HLA haplotype of the donor and recipient of the transplant, procedures that elevate the cost, which is also increased by the highly specialized workforce, such as subspecialist surgeons, such as neurosurgeons and cardiovascular surgeons, who are trained to take the stem cells in large quantities to the specific anatomical sites where they are required, through advanced surgical procedures rgicos (Sánchez-González DJ, Trejo-Bahena NI. Histology practices. Editorial Bishop; Mexico City, 2007).

Therefore, in order to eliminate these and other drawbacks, the development of the present invention that we have called "Compound of Cellular Regeneration" ("CRC") was considered, which we consider a novelty and is intended to protect by means of of the present application, since it is a compound composed of four bottles in which various base solutions ("A", "B", "C" and "D") are sequentially prepared, in which they are also suspended cellular elements (stem cells in a state of cryopreservation), which could be grown in media for this purpose; with or without (feeder cells) stored and preserved at a temperature of minus one hundred ninety- six degrees centigrade (-196 ° C). The "CRC" can also be enriched with or without the powder derived from the same amount of stem cells which are dehydrated by conventional lyophilization methods. The "CRC has the purpose of being a compound for cellular regeneration which is used in diverse medical protocols of cellular therapy of level III, with application in the field of the Regenerative Medicine and the Anti-aging The characteristic details of this invention entitled "Compound of Cellular Regeneration" ("CRC"), are clearly shown in the following description and in the three accompanying drawings.

Figure 1 shows a scheme of the invention, Figure 2 refers to the results obtained after applying "Cell Regeneration Compound" ("CRC"), in experimental animals (rats Wistar strain with Diabetes Mellitus induced by streptozotocin), In this experimental model, a selective destruction of the beta-pancreatic cells is induced, causing an insufficiency of insulin that manifests itself with the increase of blood glucose in concentrations higher than 200 mg / dl, after 4 weeks of deterioration evolution of renal function (decrease in creatinine clearance) is evident, however the treatment with "CRC" showed a cell regeneration effect of 50.27%, which was evidenced in the increase in renal function from 1.84 to 3.7 measured by creatinine clearance (ml / min) and morphological analysis of the histological sections of the glomeruli. Figure 3 presents a graph elaborated with the results of the clinical laboratory (average and standard error of the mean) obtained clinically in one of the group of our patients who presented as a common factor, chronic renal failure, where the unprecedented and statistically significant increase in renal function, after receiving the treatment with "CRC," which is quantified with studies of creatinine clearance in urine of 24 hours (ml / min), there being a total consistency between the results obtained in animal experiments with those obtained in human patients, in both cases the improvement in renal function by cell regeneration was observed after receiving the treatment with the "CRC", unpublished event and never before published, until the present patent application, all of them are examples that demonstrate the novelty and effectiveness of our invention. Figure 1 shows the drawing that outlines the procedure that allows to prepare the "CRC", likewise are indicated some conditions and elements that are required in its preparation. No. 1 indicates the cell culture boxes with pluripotent stem cells of human origin, which are cryopreserved -198 ° C, which must be thawed gradually increasing the temperature at a speed of approximately 2 degrees centigrade per minute (? 2 ° C / min.) Until reaching minus twenty degrees centigrade (-20 ° C). 5 The No 2 of Figure 1 shows the second source of stem cells which are in powder form since they were previously dehydrated by conventional lyophilization processes. The No 3 of Figure 1 shows that both sources of stem cells must be hydrated with the solution "A" which must be found at a temperature of 8 ° C. The No 4 of Figure 1, is the first base solution of the "Cell Regeneration Compound" ("CRC") which is the solution called "A". This solution must be prepared under sterile conditions and in an environment 10 controlled at a refrigeration temperature of less than sixteen degrees centigrade (<16 ° C) and greater than four degrees centigrade (> 4 ° C). The base solution "A" of the "CRC", is prepared with a liter of bidistilled pyrogen-free water, in a glass or plastic bottle with rubber stopper which is subjected to a traditional process of sterilization such as that of the autoclave, in which sodium chloride (NaCI), sodium lactate (NaCaHsOa), calcium chloride (CaC) and potassium chloride (KCI) were previously dissolved to reach the following ionic ratio: Na * = 15 130 mEq, Cl- = 109 mEq, lactate = 28 mEq, Ca2 + = 3 mEq and K- = 4 mEq; this solution must reach an osmolarity of 273 mOsm / L, and must not exceed 300 mOsm / L which is verified using a conventional osmometer. After sterilizing this solution by any conventional method of sterilization, a sterile solution is added with 55 mg of zinc chloride, 16.9 mg of cupric sulfate pentahydrate, 38.1 mg of magnesium sulfate, 13 mg of sodium iodide, 14 mg of Sodium fluoride, 163.9 mg of sodium chloride, 10 mg of 20 thiamine, 250 mg pyridoxine, 1000 mg ascorbic acid, 1.0 mg activin, 0.2 mg pluripotent cell stimulating factor (C-kit), 0.6 mg procaine derivative G1, 0.4 mg procaine derivative G2, and 0.4 mg of procaine derivative G3. The No 5 shows the prehydrated stem cells in the base solution "A", which must be evaluated in the confocal microscope, which uses a laser light source (lasser No 5), which makes it possible to make various cross-sectional images of the stem cells (No 6) (Ordóñez RM, Espinosa AM, Sánchez-González DJ et 25 al. Enhanced oncogenicity of Asian-American human papillomavirus 16 is associated with impaired The repression of E6 / E7 oncogene transcription. J Gen Virol 2004; 85: 1433-1444), which are reflected and focused by the optical lenses (No. 7) emitted by the cells in suspension with the base solution "A" (No. 8) obtaining diverse images microscopic (No. 9) (Floriano-Sánchez E, Villanueva C, Medina-Campos ON, Rocha D, Sánchez-González DJ et al., Nordihydroguaiaretic acid is a potent in vltro scavenger of peroxyriitriete, singlet oxygen, hydroxyl radical, superoxide anion , and hypochlorous acid and prevent in vivo ozone-induced tyrosine nitration in lungs Free Radie Res 2006; 40 (5): 523-533). Stem cells with healthy morphology are taken in a sterile syringe (No. 10).

In No. 11 of Figure 1 refers to the detailed morphological study that discards membrane alterations, infection, genetic alterations, karyotype and normal morphology. (Ordóñez RM, Espinosa AM, Sánchez-González DJ et al., Enhanced oncogenicity of Asian-American human papillomavirus 16 is associated with impaired E2 repression of E &oncogene transcription, J Gen Virol 2004; 85: 1433-1444).

No. 12 of Figure 1 refers to the quantification of the number of cells per milliliter of base solution by various methods of confocal microscopy or by cytomerotherm flow (FACs) in which approximately 1000, 000,000 stem cells are suspended in 500 ml of the base solution "A" of the CRC previously described.

The No 13 of Figure 1 refers to the second base solution "B" of the CRC; useful for inducing cellular regeneration by chondrogenesis, hematopoiesis and osteogenesis. Which is prepared in the following way: 500 ml of base solution "A" of the CRC with a concentration of 2000, 000 cellular elements (stem cells) quantified and previously verified by morphological analysis in confocal microscopy, at this volume (500 ml) we add: L-cysteine 1.0 mg, 0.5 g of interleukin 7 (IL-7), 0.5 g of Interieucine 3 (IL-3), 0.1 mg of Mesodermal Growth Factor A1 (FGM), 0.1 mg of monocyte colony stimulating factor (M-CSF), and 0.1 mg of granulocyte colony-stimulating factor (GM). -CSF); all added and mixed in a controlled manner under sterile conditions stored at eight degrees Celsius (8o C) for no more than a week, or at least four degrees Celsius (-4 ° C) for no more than five weeks or minus twenty degrees Celsius (- 20 ° C) for no more than twenty-four weeks.

The No 14 of Figure 1 refers to the third base solution "C" of the "CRC"; useful for inducing cellular regeneration by angiogenesis and vasculogenesis. Which is prepared in the following way, 500 ml of base solution "B" of the previously prepared CRC to which is added the following: to which is added 0.3 mg of growth factor beta (TGF-B) and 0.2 mg of endodermal growth factor K2 (FGE); all added and mixed in a controlled manner under sterile conditions stored at eight degrees Celsius (8o C) for no more than a week, or at least four degrees Celsius (-4 ° C) for no more than five weeks or minus twenty degrees Celsius (- 20 ° C) for no more than twenty-four weeks. No. 15 of Figure 1 refers to the fourth base solution "D" of the "CRC: useful to induce cellular regeneration by neurogenesis, angiogenesis and vasculogenesis, which is prepared as follows, 500 ml of base solution" C " of the "CRC" previously described to which is added the following: 100 mg of retinol, 0.5 mg fibroblast growth factor (FGF) and 0.2 mg of neurological growth factor (FGFN).

Finally the "Cell Regeneration Compound" 'CRC ") for application in Cell Therapy, Regenerative and Anti-Aging Medicine is integrated by the four base solutions (" A "," B "," C "and" D "), forming a composition fluid composed of a concentration of 2 x 109 hydrated stem cells, previously analyzed and quantified by confocal microscopy, which is prepared by adding various substances at the concentrations and conditions already described (oligometals, fortune-telling, fibroblast growth factors) The formula and procedure to prepare the "CRC" allows to apply pluripotent stem cells without any genetic modification, which are cryopreserved or lyophilized in vials or boxes of cell lines in culture, after thawing them gradually from -20 ° C to 8 ° C , are prehydrated in the base solution of the cell regeneration compound (base solution "A") which is the base solution for preparing the cell regeneration compound (bottles "B", "C" and "D").

The "CRC" (in its base solutions "B", "C" and "D") serve as inducing compounds of the stem cells in cell therapy protocols, favoring their regenerative and anti-aging capacity. The application of the process for preparing the cell regeneration compound (flasks "A", "B", "C" and "D") includes sterility conditions, morphological analysis and the quantification of stem cells.

The application of this "CRC" in cell therapy No 16 and No 17 figure 1 (bottles "A", "B", "C" and "D") allows cell therapy with stem cells to be very safe and does not require of gene typing studies for HLA haplotypes because both the base The cell regeneration compound (flasks "A", "B", "C" and "D") serves as a vehicle for transporting stem cells in cell therapy protocols , regenerative medicine and anti-aging useful for various chronic degenerative diseases, which require a cellular regeneration such as: Chronic Renal Insufficiency; Diabetes Mellitus, osteoarthritis, Parkinson's Disease, Vitiligo, etc. For which it is required to apply a minimum of five intravenous injections every 7 days of 6 ml of the cell regeneration compound using "2 ml of bottle" B ", 2 ml of bottle" C "and 2 ml of bottle" D " in addition to applying a volume of 1.0 ml intramuscularly in the deltoid region of compound "B" and if necessary 3 ml more of the cell regeneration compound, using a volume of 1 ml of bottle "B", 1 ml of bottle "C" and 1 ml of the bottle "D" this volume is applied locally in the site that is intended to regenerate.

The "Cell Regeneration Compound" ("CRC") is prepared as a sterile compound, in a liquid state with a transparent color, with its generis odor ready for paraenteral administration, which has different shades of red, ready to be applied to through injections through different administration routes, having its main application in the level III cellular therapy in Regenerative and Anti-Aging Medicine. (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Cell Therapy with Stem Cells and Regenerative Medicine.; Mexico City, 2008). For which as already described in the text and in the Figure 1, it is required to follow the procedures for its elaboration following the quantities of each substance indicated above that allows to elaborate the four base solutions ("A", "B", "C" and "D"), which conform our denominated invention "Compound of Cellular Regeneration" ("CRC") The "CRC" can be defined as a biotechnological composition of pharmaceutical grade, which is in the liquid state integrated by a concentration of 2 x 109 pluripotent stem cells, previously analyzed and quantified by procedures Confocal microscopy, the "CRC" is prepared by preparing four base solutions "A'V'B'V'C" and "D" in which various substances are added at the concentrations and conditions described above: which include : various chemical compounds, activine, fibroblast growth factors (FGF), Beta Transformation Factor (TGF-β), ascorbic acid, thiamin, riboflavin, Neurological Growth Factor, retinol, G1 procaine derivative, G2 procaine derivative, G3 procaine derivative, L-Cysteine, Mesodermal Growth Factor A1 (FG), K2 endodermal growth factor (FGE), Pluripotent cell stimulating factor (cKit), Interleukin 7 (IL-7) , interleukin 3 (IL-3), Monocyte Colony Stimulator Factor (M-CSF) and Granulocyte Colony Stimulation Factor (GM-CSF). The "CRC must be prepared in sterile disposable containers with a rubber stopper, whenever you want to introduce or remove any of the aforementioned compounds you must use sterile syringes and needle, following asepsis and antisepsis procedure (cleaning the rubber stopper with swab with alcohol of 96 °) and stored at a temperature of 0 to 8 ° C, the "CRC" should be applied intravenously immediately using a volume of 5 to 6 ml (Figure 1 No 16), the volume of "CRC which is injected should be at a temperature of 4 to 8 ° C, in the same session is applied intramuscularly in the deltoid, quadriceps or gluteal region a volume of 0.5 to 1 ml of the "CRC" (see Figure 1 No 17), the "CRC" must be stored at a refrigeration temperature of -2 ° C to 4 ° C, it has an expiration period of 30 days, if it is not frozen or refrigerated, it should not be used.

The injection of the "CRC" has shown to be very safe, which we have confirmed after seven years of basic research and three of technological development, applying it in more than 700 patients, who received the above-described scheme using a volume of 6 milliliters intravenously and 0.5 milliliters intramuscularly on ten occasions with intermediate periods of 7 days between application and application, none of the patients presented any complication, allergic reaction, anaphylactic and it was not necessary, the use of operating rooms, was never required of the interventionist radiology support to try carry the "CRC" closest to the lesion, all injections were made in peripheral veins of the upper extremities, intensive therapy was not required, and after three years all the patients improved their symptoms sufficiently so that the improvement was notorious for the patient; with regard to cell regeneration and improvement in their quality of life. After testing our invention, we consider that "CRC" is currently the only real option for cell regeneration for incurable diseases. The "CRC" is a source of replacement of dead cells, devitalized cells and cell regeneration in diseased tissues, prolong and improve the quality of life in healthy or sick people.

In Figure 1 in No. 16 and No. 17, they refer to the protocol that must be followed to apply the injections with the "CRC", once the four base solutions "A", "B", "have been prepared". C "and" D "; described previously. The "CRC" can be applied by several routes of parenteral administration, at a dose of 0.1 milliliters per kilogram of weight, generally five intravenous injections are used (No. 16) with a volume of 5 to 6 milliliters of the "CRC" and five intramuscularly, preferably in the deltoid region (No. 17); Injecting 0.5 milliliters of the "CRC" every 7 days, clinically observed cell regeneration effects from the third week of application. The constituents of the base solution "D" allow to induce neurogenesis, the constituents of the base solution "C" facilitate the hematopoiesis, chondrogenesis and osteogenesis and the constituents of the base solution "B" favor the induction of vasculogenesis and angiogenesis that can be evaluated on the skin, tests of The "Compound of Cellular Regeneration" (CRC), works by being injected in various conditions and diseases of a chronic, degenerative or aging nature; obtaining better results in patients, in which the disease or condition has been the result of destruction and / or dysfunction of a cell line; as is the typical example of Parkinson's disease, the result of the destruction or degeneration of brain dopaminergic neurons that cause characteristic motor alterations. Another typical example in which the effect of cell regeneration of the "CRC" injection has been proven is the absence or destruction of melanocytes characteristic of Vitiligo spots. And the normalization of hyperglycemia figures in patients with Diabetes Mellitus, a disease that is triggered as a result of the destruction or degeneration of pancreatic B cells, in whose evolution there are also various chronic complications, among which chronic kidney failure due to nephropathy diabetic is of transcendental importance. These conditions can be treated with the "CRC", to try to induce vasculogenesis, angiogenesis, neurogenesis and myogenesis, which allows to revert to a greater or lesser extent the natural history or clinical evolution, especially in patients with chronic renal failure, which It is progressive and irreversible, since it has a loss of endothelial, glomerular and tubular cells, renal function, as well as the disappearance of neurological symptoms, inflammation and joint pain that occur due to biological aging and the development of chronic degenerative diseases. This cycle of ten injections of the compound can be used two to three times to complete thirty injections over a period of four months. The circulating stem cells released by the "CRC" can be incorporated into undamaged organs, and act as anti-aging agents, by increasing the average life of the cells of the organ and the person in question (Méndez-Bolaina E, Sanchez-Gonzalez DJ et al., Effect ofcaveoHn-1 scaffolding peptide and intracellular Ca2 + klnetics evoked by angiotensin // in human vascular smooth muscle cells Am J Physiol Cell Physiol 2007; 293: C1953 - C1961). The object of developing this invention was to provide a compound that induced cell regeneration, a non-existent invention in the market, using pluripotent stem cells of human origin in suspension activated by the "CRC" components for application in the form of cell therapy. , avoiding gene studies HLA typing, and surgical and interventional radiology interventions that are used in the implant or cell transplant.

The "CRC" acts using the principle of cell regeneration, which naturally occurs in the tissues of the body, this becomes evident when considering that throughout life the organisms suffer from a continuous wear, if there was no regeneration cellular life, the life expectancy of living beings would be reduced significantly. On the other hand, much of the broad range of diseases that affect humans, have their origin in the degeneration and death of different types of differentiated cells that make up the tissues and organs of our body, which are affected in a harmful way acutely as it usually occurs in acute myocardial infarction or chronically as in degenerative diseases and biological aging.

The "Cell Regeneration Compound" ("CRC) facilitates intravenous, intramuscular and local administration in cell therapy protocols, strengthening the intrinsic capacity of the patient's endogenous stem cells, such as those received as external stem cells from the patient's injection. "CRC" by extrinsically providing a sufficient supply of pluripotent, healthy, non-tumor-forming stem cells, activated and directed to the differentiation for specific therapeutic purposes in chronic degenerative diseases in which chronic kidney failure and Diabetes Mellitus are included. After describing its composition and way of preparing the "Compound of Cellular Regeneration", the inventors Gerardo Martín González-López, Dolores Javier Sánchez-González and Carlos Armando Sosa-Luna, claim the "Compound of Cellular Regeneration". ("CRC") as his invention, declaring that to his real knowledge and understanding they have described in the simplest form, the way to carry it out his invention. In several recent scientific publications noted above in the background of the present patent application, it has been clearly concluded that increasing the number of stem cells in the circulation is becoming one of the best indicators of health in humans. Objective that is achieved safely by applying the "Cellulaf Regeneration Compound (" CRC "), broadly described in the present invention application. (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Cell Therapy with Stem Cells and Regenerative Medicine, Editorial Alfil, México Distrito Federal, 2008).

OPERATION OF THE INVENTION The main objective of the "CRC" is to be an assistant in the treatment of chronic, degenerative and anti-aging diseases. The aggressions of the environment contaminated by human industrialization, accelerate considerably the decline in the reserve of endogenous stem cells, and therefore the capacity of intrinsic cell regeneration of patients or elderly people is diminished, limiting their health and longevity (Trejo -Bahena NI, Pérez-Astudillo LH, Oquela-Henry DJ, Balderas-Cornelio A, Salinas-Cano F, Martínez-Martínez CM, Sánchez-González DJ.Comparative study to determine hippuric acid (HA) in urine by colorimetric methods Ogata and Astudillo, Rev Sanid Milit Mex 2008; 62 (1): 35-41).

In various recent scientific publications noted above in the background of the present patent application, it has been concluded that the number of stem cells in the blood is one of the best indicators for health in humans. Therefore it was required to invent a compound that allows the introduction of pluripotent stem cells, in the blood of patients with incurable, chronic, degenerative or elderly diseases, this is achieved safely by applying the "Compound of Cellular Regeneration ° (" CRC "), broadly described in the present invention application (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Stem Cell Therapy and Regenerative Medicine, Editorial Alfil, Mexico City, 2008). invention: "Compound of Cellular Regeneration" ("CRC") is explained because the CRC injection increases the stock of stem cells, strengthening the intrinsic capacity of cell regeneration in patients and even in healthy people in which a effect of biological anti-aging, obtaining a better state of health and quality of life, which can be evidenced in many ways, of this there is no doubt, since every day the number of investigations increases, which prove that the stem cells in circulation are the most important factor in the health of the people, which allows cell regeneration, so that the greater the number of stem cells in circulation, the greater the ability of the body to regenerate, that we have been able to record since a dose-dependent effect is observed with the "CRC" in our patients. (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Cell Therapy with Stem Cells and Regenerative Medicine, Editorial Alfil, México Distrito Federal, 2008).

The base solutions "A", "B", "C" and "D" of the "Cell Regeneration Compound" ("CRC") work by activating and inducing the proliferation, tropism and transdifferentiation of pluripotent stem cells that function as micro- intelligent spheres with the entire human genome without any genetic modification, which are introduced into the circulation or a tissue through a sterile liquid suspension that allows to carry in a suitable volume 6 to 0.5 milliliters (mi) a sufficient number of pluripotent stem cells (10,000,000 as well as its cellular products, reaching the circulation and the target organ in the safest and most practical way, increasing the number of stem cells and the regenerative capacity in diseased organs that have access to the systemic circulation and when this is diminished perform injections or applications locally, using various routes of pharmacological administration, such as: intravenous, intramuscular and the local (interarticular, ophthalmologic, topical, etc.). (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Cell Therapy with Stem Cells and Regenerative Medicine, Editorial Alfil, México Distrito Federal, 2008).

The intravenous application of the "Compound of Cellular Regeneration" ("CRC"), allows a rapid release and the intramuscular route allows a slow release, which, being handled intelligently, allows pluripotent stem cells to reach the site of the lesion or target organ. sick or aged, in which various bioactive molecules are expressed and released that attract pluripotent stem cells to reach the site where they are needed by stimulating their transdifferentiation. The base solutions promote the activation of the necessary elements so that these processes of cellular regeneration are carried out, the injection of the "CRC" facilitates the entrance of the pluripotent stem cells to the damaged tissues and accelerates the differentiation processes, since the cells mother acquire the characteristics of the differentiated cells that make up the tissue of the target organ, the "CRC" allows pluripotent stem cells to be implanted more quickly.

The "CRC" stimulates the endogenous stem cells (proper to the patient functioning as an autogenic transplant) and the exogenous pluripotent stem cells (released in the "CRC" injection functioning as an allogeneic transplant). Stem cells derived from the patient together with those that are released by the "CRC" can be incorporated into organs damaged by the process of tropism and transdifferentiation. These processes are carried out more easily due to the bioactive action of the different compounds with which the "CRC" is elaborated. The pluripotent stem cells are activated by the bioactive molecules contained in the "CRC" and produce more bioactive molecules of cell regeneration and once the damage has been resolved or repaired by replacing the number of cells deficient in the parenchyma of the diseased or insufficient organ ( kidney, heart, nervous system, blood, immune system, joint, etc.). The "CRC also act as an anti-aging agent, which provide bioactive molecules of cellular regeneration to devitalized cells, increase the average life of the cells of the organ and the organism in question, this is done through a mechanism known as horizontal inheritance , the stem cells in the diseased or aged site can donate their intracellular molecules from both the nucleus and the cytoplasm to cells devitalized by aging or disease (González-López GM, Sánchez-González DJ and Sosa-Luna CA. Stem Cell Therapy and Regenerative Medicine, Editorial Alfil, Mexico City, 2008).

The "Compound of Cellular Regeneration" ("CRC") works as an injectable solution that has the therapeutic effect of inducing: hematopoiesis, vasculogenesis, angiogenesis, myogenesis and neurogenesis, the cell regeneration effect that we have studied the best is the kidney, the which has become evident our investigations of chronic renal failure and nephroprotection, which is widely exemplified in the present patent application (Figures 2 and 3).

In Figure 2, some results of our experiments are presented applying "Compound of Cellular Regeneration" "CRC (Cell Therapy) in animals with renal insufficiency in an experimental model of Diabetes Mellitus in our laboratory with insulin insufficiency, in rats of the strain hyperglycemic (blood glucose above 200 milligrams per deciliter (mg / dl)), injecting a solution with streptozotocin at a rate of 60 milligrams per kilogram of weight of the rat by paraenteral route.The application of the "Compound of Cellular Regeneration" CRC "(Cell Therapy) intravenously and intramuscularly in diabetic rats with chronic renal failure, allowed to regenerate damaged kidneys, evidenced by the increase in creatinine clearance (No 10) and morphological analysis (No 5). that in the black bar (healthy laboratory animals or control No 2 and No 4) have an average creatinine clearance of 2.84 ml / min equivalent to a kidney function of 94.66% while the laboratory animals represented by the red bar ill with Diabetes Mellitus (No 8 and No 6), without any treatment during the evolution of hyperglycemia) showed an average creatinine clearance of 1.84 ml / min, equivalent to a renal function of 61.3%, which makes it possible to extrapolate the diagnosis of chronic renal failure in humans (<; 70%). The sick animals represented by the green bar (No 9) with Diabetes Mellitus who received a standard nephroporotector treatment with an angiotensin-converting enzyme inhibitor drug; ramipril at a dose of 1 mg / kg of weight daily orally showed a creatinine clearance of 2.6 which corresponds to a renal function of 86.6% and sick animals with Diabetes Mellitus represented with a yellow bar (No 10) who received the " Compound of Cellular Regeneration "(Cell Therapy) showed a creatinine clearance of 3.7 ml / min equivalent to a kidney function of 123.3%, a cell regeneration was obtained (No 5). The animals with Diabetes Mellitus referenced in the blue bar (No 11), received a treatment with selective inhibitor of cyclooxygenase in their isoform 2 (celecoxib) at a dose of 4 milligrams per kilogram of weight daily orally, presented an effect nephrotoxicity (No 7), observing the presence of frank proteinuria in the Bowman capsule, a creatinine clearance of 1.4 milliliters per minute equivalent to a renal function of 46.66% in frank renal failure., manifesting clinically, with hypertension, decreased of creatinine clearance, proteinuria, normocytic-normochromic anemia, morphological findings of diabetic nephropathy; in addition to peripheral vascular disease, with venous or arterial insufficiency, ulcers and infections that are difficult to heal in the lower extremities, a condition known as diabetic foot. (Sosa Luna CA et al., Rev Sariid Milit Mex 2005 59 (1): 32-50 and Rev Sanid Milit Mex 200660 (5): 324-333), other conditions in which we have observed that the application may be useful of the "CRC" are: sickle-cell anemia, thalassemia, muscular dystrophy, dementias, Alzheimer's disease, epilepsies, schizophrenia, cerebrovascular disease, (Sosa Luna CA et al Rev. Sanid Milit Mex 1999; 53 (2): 123 -128 and Sosa Luna CA et al., Rev. Neurology, Neurosurgery and Psychiatry 2002; 35 (4): 183-202) traumatic spinal injuries, herniated discs, degeneration of Purkinje cells, cardiac ischemia, liver failure , venous insufficiency, peripheral arterial insufficiency, Duchenne muscular dystrophy, osteoarthritis, osteogenesis imperfecta, Down syndrome, hypothyroidism, rheumatoid arthritis, osteoarthritis, osteoarthritis, systemic lupus erythematosus, vitiligo, as a support for regeneration in cancer patients who are receiving schemes radio therapy and chemotherapy, etc. (Vásquez-Moctezuma I, Meraz-Ríos MA, Magaña M, Villanueva-López GC, Sánchez-González DJ, Chemoresistance in melanoma, Preliminary report, Dermatol Dermatopatol 2006; 6: 8-10 and Torres-Salazar JJ, Sánchez- González DJ et al., Distribution and state of maturation of dendritic cells and activation of CD4 + lymphocytes in prosthetic adenocarcinoma Rev Mex Urol 2007; 67: 140-146) The "CRC" has an anti-aging effect, this is explained because as the age of the persons advances, in the body of the same the number of stem cells in circulation is lower and in the organs they become more scarce, conditioning a greater vulnerability in health, which is common to observe in the elderly. If we inject the "CRC" in the circulation of these patients, the number of available stem cells in the circulation and organs increases. Intravenous and intramuscular injection of "CRC in elderly and patients allows to increase their capacity for cell regeneration, patients report decreased fatigue and fatigue, in the circulation increases the number of stem cells injected with the" CRC, these are they are activated by migrating from the circulation to organs, devices and systems that are old and insufficient. As we already pointed out, the release of exogenous pluripotent stem cells released by the injection of "CRC facilitates their transdifferentiation in different types of differential cells such as: the endothelial cells and others that make up the organs and tissues of the body, with improvement observed in the elderly dependent on cellular regeneration that is reflected in the skin, greater hydration, luminosity, skin turgencias, as well as the elderly perceive a state of revitalization (recovery of energy) to the elderly (Tapia E, Sánchez-González DJ, et. al. Treatment with pyrrolldlne dithlocarbamate improves proteinuria, oxidative stress and glomerular hypertenslon in overload proteinuria Am J Physiol Renal Physiol 2008 Aug 27).

Protein damage can be better explained by a poor diet (rich in carbohydrates, poor in amino acids and proteins) and damage to the mitochondria, which also deteriorate over time, although they do not always do so consistently. When the damage exists, it is possible to demonstrate it structurally with a high resolution confocal microscope (Sánchez-González DJ et al.) Confocal microscope in the dermatological diagnosis of autoimmune bullous diseases Acts Dermatol Dermatopatol 2007; 7: 9-15 e Microscopy images confocal in the diagnosis of autoimmune bullous diseases Rev Sanid Milit Mex 2006; 60 (2): 82-90).

Aging from the biological point of view is studied in the chromosomes with confocal microscopy, in the cellular senescence crosslinks of the deoxyribonucleic acid (DNA) are observed and often breakages of a single chain take place; they diminish DNA methylations and losing the telomeric sequences in said nucleic acid. The pluripotent stem cells used to elaborate the "CRC" do not present these alterations of cellular senescence and on the contrary the telomeric sequences of the pluripotent stem cells are elongated and healthy (Figure 1). Aging also adds to environmental aggression (which includes various infections, accidents, injuries and other diseases whose origin and physiopathology is not yet known), as well as endogenous aggression which is divided into the DNA alterations inherited by our parents, which is associated with the onset of chronic degenerative diseases such as diabetes mellitus, hypertension, cancer etc. (Pou-López VC, Gallardo-Ollervides FJ, García-Mendoza JA, Sánchez-González DJ, Transtympanic dexamethasone in sudden sensorineural sudden hearing loss Rev Sanid Milit Mex 2008; 62 (2): 57-65). These aggressions continue with the series of harmful impacts, although the primary structure of the proteins does not change with the aging of the DNA, the environmental and endogenous aggressions increase the changes after the translation (Sánchez-González DJ et al. induces NOS expression and tyrosine nitration in rat aorta Environ Toxicol Pharmacol 2004; 17: 1-7 and Sánchez-González DJ et al. Production of NOS and nitration of proteins in the aorta of rats exposed to ozone Rev Sanid Milit Mex 2005; 59 (4): 223-240). The cellular regeneration, with the periodic application of intravenous and intramuscular injections once a week with "CRC", is more evident, when due to some disease, a differentiated cell line, is under a great challenge or stress, such is the case of insulin-producing cells known as B cells of the islets of Langerhans of the pancreas, which are diminished or destroyed in patients with Diabetes Mellitus, causing a sensation of chronic fatigue, and when insulin insufficiency is caused, observed the increase in blood glucose, appearing increased urine, thirst and increased appetite, characteristic symptomatology of this disease (Shamblott MJ, Clan GO, Cell therapies fortype 1 diabetes mellitus Expert Opin Biol Ther2004 Mar; Vol. 4 (3 ), pp. 269-77).

It should be noted that the effect of cell regeneration observed with the injection of "CRC" is a phenomenon that, on a smaller scale, occurs naturally, especially in young and healthy organisms. Naturally, endogenous stem cells are released physiologically from the bone marrow and other reservoirs (oval cells of the liver, satellite cells in the muscle, cells of the crypt in the digestive tract, among others); crossing the bloodstream towards those tissues that have the greatest need. When an organ is subject to demands due to illness, this organ triggers compounds that emit a signal so that the stem cells are released into the circulation. The organ initiates the cascade of inflammation by releasing into the circulation compounds that attract stem cells to this particular organ. Then the stem cells that were released by our cell regeneration compound, follow the path of concentration of these compounds and leave the bloodstream to migrate to the organ where they are proliferating and begin to differentiate into cells of that particular organ The ability of the "CRC" to release the activated stem cells in the circulation to Through our invention and the described cell therapy protocols for regenerative and anti-aging medicine are of great relevance since the circulating stem cells decrease with increasing age and in chronic and degenerative diseases (Pacheco-Ramírez MA, Rodríguez-Perales MA, López-Chavira A, Canul-Andrade LP, Martínez-Martínez CM, Sánchez-González DJ, Expression of nitric oxide synthases in glomus tumors of the head and neck Rev Sanid Milit Mex 2006; 60 (6): 369-378). In this way, it could be concluded that children and babies have a very effective "stem cell system" and do not need the support of the "CRC". However, we have injected the "CRC" in children under 10 years of age in support of the treatment of chemotherapy and radiotherapy in acute leukemia, as well as in pediatric patients with genetic syndromes such as Down syndrome, Turner, etc. Observing improvement in its symptomatology. Also in children with neurodevelopmental problems, autistic, mental weakness, infant cerebral palsy, attention deficit and young people with schizophrenia. (Aguilera-Hernández P, Chánez-Cárdenas ME, Sánchez-González DJ et al.) Regulation of nitric oxide synthases in rat striatum in the model of Huntington's disease induced by quinolíníco Arch Neurocien Mex 2006; 11: 31).

Cell therapy using the "CRC" is the safest way to treat the damage suffered by the genetic material found in the cell nucleus and mitochondria. These damages are one of the most relevant factors in the process of biological aging and cellular senescence. In the elderly there is a greater number of structural alterations of chromosomes (genetic material) which are composed of deoxyribonucleic acid (DNA) that manifest with the symptoms of aging such as deterioration of cardiovascular function, osteomuscular, presbycusis and presbyopia, etc. (Béjar-Cornejo F, Olivares D, Cantero MA, Sánchez-González DJ, Corneal thickness determined by ORBSCAN corneal topography in patients diagnosed with glaucoma in the Mexican population Rev Sanid Milit Mex 2007; 61 (5): 310-319) mother contain intact DNA as well as healthy mitochondria and many proteins that have the ability to reverse many of the effects of aging, stem cells are rich in the telomerase enzyme which can decrease the loss of telomeric DNA sequences in aging cells or senescent From the point of view of "gene therapy", we can consider that stem cells are the best vector, and can be considered as "intelligent microspheres" (since they are living microscopic organisms, with the total capacity of self-replication as well as tropism, that is, recognize and travel to the site of damage or injury, as well as transdifferentiation of difference in the missing or injured cell type) (Sánchez-González DJ et al.Effects of electromagnetic fields of industrial frequency.) Model in rats. Sanid Milit Mex 2007; 61 (6): 371-380). Since they contain in their interior the complete human genome, which, unlike the protocols of gene therapy, is intact, undifferentiated and can give rise to all the proteins that give origin to the diverse cell types that constitute the human body, It should be noted that in cell therapy with stem cells, non-negative stem cells have been modified, altered or even touched in their genetic machinery (DNA), they have only been protected from all the aforementioned harmful agents such as irradiation, infectious agents, etc. So the cells that are transplanted have a biological age of zero years (new).

Here are several examples of the use of the "Cell Regeneration Compound" ("CRC"): Example 1: Injection of "CRC" in chronic diseases and neurodegenerative diseases. This group of clinical entities is diagnosed more and more frequently in our country and in the world. These diseases group Alzheimer's dementias, Parkinson's disease, Huntington's disease and Amyotrophic Lateral Sclerosis (Aguilera P, Sánchez-González DJ et al., Time-related changes in constitutive and inducible njtric oxide synthases in the rat. striatum in a model of Huntington's disease, Neurotoxicology 2007; 28 (6): 1200-1207). The peculiarity of these clinical entities is that they do not have a treatment that has the ability to limit the progression of the disease or to reverse the severe deterioration and disability that occur during its natural history. They have an invariably progressive, incapacitating course and can cause short-term mortality in some occasions, however, the disability is significant in all of them. Given the little curative effect of the current pharmacological treatments of conventional medicine, we have explored the application of "CRC" as a therapeutic alternative. Brain repair ugh the application of cellular transplants has been the focus of attention in recent research. Additionally, the nervous system has immunological privileges that reduce the need for the usual immunosuppressants in transplants, even in heterologists. The "CRC" has been useful to revert the symptoms in patients with this type of diseases after 15 to 10 injections of "CRC" showing improvement from the 10th injection of the "CRC". In the neurodegenerative diseases, from the years 2001 and 2003, the results of controlled studies of transplantation of dopamine neurons of embryonic origin in patients with light-moderate Parkinson's disease were reported. Previously neurosurgeons had concluded that the application of multiple implants, including the substance nigra and striatum in animal models produced better results. Likewise, we showed how the "CRC" is useful for the treatment of this type of patients, which showed clinical improvement as well as with the use of single-pulse TECT emission tomography Tc99m ECD and without developing motor complications or major .

The objective of injecting the "CRC" is to implant through the circulation stem cells in Parkinson's disease, which allow reconstructing the nigrostriatal neuronal pathway, once the neural stem cells arrive they differentiate into dopamine-producing neurons . The transplantation of dopaminergic neurons derived from stem cells stimulates local synapses with the subsequent release of dopamine. Patients with neurodegenerative diseases such as Parkinson's improve clinically with the treatment of human stem cells released in the "CRC" decreasing the generalized awkwardness and the slowness in performing movements; improving the shortage of spontaneous motility, decreases resting tremor and rigidity [Sánchez-González DJ et. to the. Nitric oxide in the central nervous system. Nitrérgicas neurons. Neurol Neurocir Psiquiat 2004; 37 (2): 73-78). Patients recover the response to the pharmacological administration of the precursor (levodopa). Today the application of "CRC" is an alternative for patients with Parkinson's. Magnetic resonance studies can be performed at the beginning and at 6 months of cell therapy, with spectroscopy of N-acetylaspartate (NAA) / creatine (Cr) and SPECT perfusion studies with Te 99m ECD. The clinical results have been very satisfactory. No complications have occurred and all patients improve their clinical parameters.

Example 2: Chronic Renal Failure and Vascular Complications of Diabetes Mellitus. Figure 3 shows a graph showing the average result of creatinine clearance before and after treatment with "CRC" in our patients with chronic renal failure. obtained from the creatinine clearance studies before (No 1) and after (No 2) receiving ten applications of the "CRC" intravenously and intramuscularly. They showed reversal in the progression of renal function deterioration in their unprecedented clinical laboratory studies and symptomatology (Cruz C, Correa-Rotter R, Sánchez-González DJ et al., Renoprotective and antihypertensive effets of S-allylcysteine in 5 / 6 nephrectomized rats Am J Physiol Renal Physiol 2007; 293: F1691-F1698 and Chirino Yl, Trujillo J, Sánchez-González DJ et al. Selective NOS inhibition reduces renal damage induced by cisplatin Toxicol Lett 2008; 176 (1) : 48-57). In figure 2 the graph was shown, elaborated with the results of our experiments performed on laboratory animals, rats strain Wistar with diabetic nephropathy by Diabetes Mellitus; induced with an intraperitoneal injection of streptozotocin. Changes can be observed at 5 weeks after treatment with "CRC", which corroborate the results of the creatinine clearance consistent with those obtained in humans in the clinical files (Pedraza-Chaverri J, Yam-Canul P, Chirino Yl, Sánchez-González DJ et al., Protective effects of garíic powder against potassium dichromate-induced oxidative stress and nephrotoxicity, Food Chem Toxicol 2008; 46 (2): 619-627 and Segoviano-Murillo S, Sanchez-Gonzalez DJ et al. S-allylcysteine ameliorates ischemia and reperfusion induced renal damage Phytother Res 2008; 22 (6): 836-840). The experiments in animals figure 2, not only allowed us to evaluate the function, but also we could observe the changes in the microscope of the glomeruli in the renal histology sections. The cuts of the control animals were similar to the cuts of diabetic rats treated with our treatment of Regenerative Medicine that is offered to patients in SITECEM (Orozco-lbarra M, Medina-Campos ON, Sanchez-Gonzalez DJ et al. -Chaverri J. Evaluation of oxidative stress in d-serine induced nephrotoxicity Toxicology 2007; 229: 123-135; Yam-Canul P, Chirino Yl, Sánchez-González DJ et al., PJ34, a poly adenosine diphosphate-ribose polymerase inhibitor , attenuates, chromate-induced nephrotoxicity, Basic Clin Pharmacol Toxicol 2008; 102 (5): 483-488 and Yam-Canul P, Chirino Yl, Sánchez-González DJ et al., Nordihydroguaiaretic acid attenuates potassium dichromate-induced oxidative stress and nephrotoxicity. Food Chem Toxicol 2008; 46 (3): 1089-1096).

Example 3: Patients with refractory angina and with a history of myocardial ischemia or infarction, when they can no longer be treated with conventional therapies such as coronary angioplasty and stenting, with an ejection fraction of 37.5% after receiving cell therapy With "CRC" they can improve their ejection fraction by 47% in less than a month and reducing medication requirements and symptoms. Patients with heart failure with functional class III and baseline ejection fraction of 30% improve after five to fifteen sessions of cell therapy with "CRC". The vast majority of patients treated with 15 injections of "CRC" will improve to a functional class II. Some of the studies of SPECT Sestamibi Tc99m to those after treatment with "CRC" during clinical follow-up show improvement by cell regeneration translated into an increase in vascularity and viability of the myocardium. Specific example of this is, one of our patients with a disease of three coronary vessels that was out of treatment by coronary angioplasty after having been evaluated by the specialist hemodynamics (Dr. Hugo Gutiérrez Leonard at the Central Military Hospital), the patient improved the myocardial perfusion SPECT Sestamibi Tc99m after receiving five intravenous injections of the "CRC", we could perceive a marked improvement evidenced by the same relatives, since now I could walk more blocks without presenting pain in the chest, fatigue and shortness of breath, the study showed ischemia in a single coronary branch, that is to say, of the three vessels with ischemia, two were regenerated, with the application of stem cells.

Example 4, application of the "CRC" in neuroregeneration: we have great expectations due to the improvement observed in patients treated with the "CRC" who have neurological disorders, such as facial paralysis in which we have had great success, injection of the "CRC" is fully justified in vascular disease (due to multiple cerebral infarcts) and in the cases of vascular dementia, Huntington's disease, fronto-temporal dementia, dementia with Lewy bodies and AIDS dementia, among others. Dementias that are clinical syndrome characterized by severe loss of cognitive and emotional skills (memory and depression) acquired that interfere with daily performance and quality of life. Dementia can be caused by more than 55 diseases, some non-progressive and occurs mainly in later stages of life. The prevalence of dementias increases as the age advances and after the age of 60 doubles every five years, to increase to 30 or 50% in people aged 85 and older. There are multiple forms of dementia; however, the most common is Alzheimer's dementia, which accounts for between 80 and 85% of the causes of dementia. Although there are several medications useful in the treatment of dementia, none of them has been effective in stopping the inevitable progression of this neurodegenerative disease. The frequency and The prevalence of this disorder increases gradually in the world. This fact is mainly due to the increase in the life expectancy of the population. An estimate made by our group of researchers in 1999 reported that in our country there was a prevalence of 814 thousand people with cognitive disorders associated with age, and more than half a million Mexicans with Alzheimer's dementia. Patients with Alzheimer's improve their intellectual capacity and memory. Autistic children and children with Down syndrome improve their ability to speak, articulate words, improving communication with their parents and teachers. Of all the cases with dementia, less than 75% are susceptible to treatment with the "CRC". We have verified the effectiveness of the application of more 5 to 10 injections of "CRC" in patients with Down syndrome, autism, deafness as well as mutes, in patients suffering from neurological sequelae due to cerebral vascular events. In all cases there is an improvement in the symptoms and signs that they present, all of these have been treated with outpatient outpatients, however, to apply cell therapy with "CRC" in patients with severe mental and psychiatric conditions, such as Chronic Schizophrenia, hospitalization is necessary with special facilities for which cooperation and research with the Mexican Association of Friends of Schizophrenic Patients AC (AMAPE).Example 5: The "CRC" has application for the treatment of osteoarthritis, herniated disc or to obtain a faster recovery after having been operated on in some surgery and to try to regenerate some traumatic injury of the spinal cord. This last application in our laboratory we did not find working in the search of the most appropriate methodology, to apply the "CRC" in the search to achieve a damaged spinal cord repair. Unfortunately young people and young adults have sequelae of different magnitude ranging from herniated discs in which the "CRC" has an excellent response to treatment as serious consequences as paralysis of the four or two extremities due to spinal cord injury caused by accidents or degenerative diseases. and congenital. Therefore, we are clinically investigating the possible local application of "CRC" in the fission zone to try to repair the damaged spinal cord.

In our country there have been no studies "CRC" traumatic injury of the spinal cord; However, it has been estimated that the annual frequency of people with spinal cord damage should be similar to that of 40 cases per one million inhabitants that occurs in the United States of America, which represents an incidence of 11 thousand cases new every year. This estimate does not include the cases of people who die in the accident.

The most frequent causes of spinal cord injury are, in a consistent manner, vehicle accidents (41%), violence injuries (22%) and falls (21%). Because the age of presentation of the spinal lesion is in young people and young adults, with potential for prolonged survival, the prevalence of this clinical entity is quite high and increases every year. It has been estimated that more than a quarter of a million people in North America currently live with disability due to sequelae due to spinal cord injury. Most cases of spinal cord trauma occur in young adults. The average age of these cases is 28.7 years; most of the spinal trauma occurred between 16 and 30 years of age. 77.8% of cases of spinal injury are male, usually young or young adults who are in the productive stage or at the beginning of it. It has been observed that more than half of the patients (64.2%) were employed before suffering spinal cord injury. After the traumatic event, only one third of the patients with Paraplegia returned to gainful employment at the tenth year of evolution. Due to the above, it is considered that this clinical entity has an important economic repercussion in the patient and in his family, due to the direct and indirect costs that it produces. The average annual cost for the health care of the patient and the direct costs, vary according to the severity of the injury. However, the indirect costs that include loss of salary, loss of supplementary benefits and productivity, are estimated to be on average around 60 thousand dollars per year; however, this figure may vary depending on the educational level of the patient, the type of employment and the work history before the accident, as well as the severity of the spinal cord injury. . We have had very good results in patients with osteoarthritis and herniated disc after applying 5 to 10 weekly injections of "CRC". For the previous, we consider justified its application of "CRC" as an alternative therapeutic option for this type of problems, when conventional treatments no longer give results.

Example 6, intravenous and intramuscular injections of "CRC can be used to slow aging (anti-aging) and in incurable dermatopathies such as that affecting the skin such as Vitiligo: in people of 60 years or more, wrinkles, gray hair, chronic tiredness , arthrosis, stooping are evident as well as the appearance of other chronic degenerative diseases, it has been seen that the application of at least 10 injections of "CRC" improves the quality of geriatric patients, reduces joint pain, in some patients blackening of the gray hair can be observed, patients perceive a greater vitality, there may be normalization in blood pressure, in the circadian cycles of sleep-wakefulness, attention, memory, appetite, muscular strength, coloration, hydration and softness in the skin. In patients with Vitiligo the "CRC" causes a red dotting, which turns pink and later the white areas of hypopigmentation are repigmented.

Example 7, the "CRC" can be applied in some people who wish to prevent or delay the appearance of diseases suffered by their relatives and even being healthy, the application of "CRC in healthy people improves fatigue, and cell regeneration of the devices and systems of the human body, in order to face surgeries and environmental aggressions, athletic patients reach the parameters or objectives that are proposed more quickly.Applying the "CRC" before being operated on in an elective surgery, accelerates the regeneration times and the healing of surgical wounds are faster, the "CRC" favors the normalization of metabolism very useful in the treatment and prevention of obesity, metabolic syndrome, etc. In children and young people with congenital defects, the application of "CRC in the growth cartilages, induces the growth of limbs that presented shortening, in patients with deformities from the n As depressions in the face, the injection of the "CRC" allows to reconstruct regions that had not been able to develop and much less ossify.

Claims (5)

CLAIMS Having sufficiently described our invention, we consider it as a novelty and therefore claim as our exclusive property, what is contained in the following clauses:

1. - The concentrations, volumes, of the different constituent elements of the compound, conditions of sterility and temperature that are described in the present application necessary to elaborate the base solutions "A", "B", "C" and "D" that make up the "Compound of Cellular Regeneration" ("CRC") that are written in the description of the invention: The base solution "A" of the "CRC", which is prepared with a liter of double-distilled pyrogen-free water, in a glass or plastic bottle with a rubber stopper which is subjected to a traditional sterilization process such as the autoclave, in which sodium chloride was previously dissolved (NaCl ), sodium lactate (NaC3H503), calcium chloride (CaCk) and potassium chloride (KCI) to achieve the following ionic ratio: Na- ^ 130 mEq, Cl- = 109 mEq, lactate = 28 mEq, Ca2 + = 3 mEq and K + = 4 mEq; this solution must reach an osmolarity of 273 mOsm / L, and must not exceed 300 mOsm / L which is verified using a conventional osmometer. After sterilizing this solution by any conventional method of sterilization, a sterile solution is added with 55 mg of zinc chloride, 16.9 mg of cupric sulfate pentahydrate, 38.1 mg of magnesium sulfate, 1.3 mg of sodium iodide, 14 mg of Sodium fluoride, 163.9 mg of sodium chloride, 10 mg of thiamine, 250 mg of pyridoxine, 1000 mg of ascorbic acid, 1.0 mg of fortune-teller, 0.2 mg of stimulant factor of 'stem cells (C-kit), 0.6 mg of procaine derivative G1, 0.4 mg of procaine derivative G2, and 0.4 mg of procaine derivative G3. The base solution "B" of the "CRC"; which is prepared with 500 ml of "A" base solution of the "CRC" with a concentration of 2000,000 cell elements (stem cells) quantified and previously verified by morphological analysis in confocal microscopy, at this volume (500 ml) is added In addition: L-cysteine 1.0 mg, 0.5 Interleukin 7 Mg (IL-7), 0.5 pg of Interieucin 3 (IL-3), 0.1 mg of Mesodermal Growth Factor A1 (FGM), 0.1 mg of monocyte colony stimulating factor (M-CSF), and 0.1 mg mg of granulocyte colony stimulating factor (GM-CSF); all added and mixed in a controlled manner under sterile conditions stored at eight degrees Celsius (8o C) for no more than a week, or at least four degrees Celsius (-4 C) for no more than five weeks or minus twenty degrees Celsius (-20 C) for no more than twenty-four weeks. And the base solution "C" of the "CRC", which is prepared in the following way: 500 ml of the base solution "B" of the "CRC" previously prepared, to which the following is added: it adds 0.3 mg of beta growth transforming factor (TGF-B) and 0.2 mg of endodermal growth factor K2 (FGE); all added and mixed in a controlled manner under sterile conditions stored at eight degrees Celsius (8th C) for no more than a week, or at least four degrees Celsius (-4 ° C) for no more than five weeks or minus twenty degrees Celsius (-20 ° C) for no more than twenty-four weeks. And the base solution "D" of the "CRC"; which is prepared with 500 ml of the "C" base solution of the "CRC" described above, to which is added the following: 100 mg of retinol, 0.5 mg of fibroblast growth factor (FGF) and 0.2 mg of factor of neurological growth (FGFN). Finally integrating the "Cell Regeneration Compound" ("CRC") ready for application in Cell Therapy, Regenerative and Anti-Aging Medicine, this reddish liquid composition must contain a concentration of 2 x 109 pluripotent stem cells not generating tumors, previously analyzed and qualified by confocal microscopy.

2. -The use of pluripotent stem cells of human origin, without any genetic modification, which are stored or lyophilized in flasks or boxes of cell lines in culture, after thawing them gradually from -20 ° C to 8 ° C, are prehydrated in the base solution "A", and of being evaluated by the methods described in the description of the invention as elements of the "Cell Regeneration Compound (" CRC ").

3. - The procedures described in the description of the invention that allows the application of the "CRC" in its manufacturing phase (base solutions "A" "B", "C" and "D" of the "CRC") include sterility conditions, temperature, morphological analysis and the quantification of stem cells in the stipulated concentration and volume stipulated in the description of the CRC. And the times and volumes of application of injections with the "Compound of Cellular Regeneration" ("CRC") written in the description that are 6 milliliters intravenous and 1 milliliter intramuscular every seven days, of the present application to be applied in medicine protocols regenerative and anti-aging without the need for gene typing studies for HLA haplotypes of pluripotent stem cells used for the preparation of the "CRC" and the patient receiving the "CRC" injection.

4. - The use of the "Compound of Cellular Regeneration" (CRC) through various weekly injections in order to treat various chronic degenerative diseases, which require cell regeneration such as: Chronic Renal Insufficiency; Diabetes Mellitus, Arthrosis, Rheumatoid Arthritis, Systemic Lupus Erltematosus, Amyotrophic Lateral Sclerosis, Multiple Sclerosis, Parkinson's Disease, Vitiligo, Herniated Disc, Down Syndrome, Autism, Schizophrenia, Dementias, Hearing Loss, Paralysis, Arterial or Venous Vascular Insufficiency , etc. For which it is necessary to apply a minimum of five intravenous injections every 7 days with a volume of 6 ml of the "Compound of Cellular Regeneration" (CRC) using "2 ml of bottle" B ", 2 ml of bottle" C "and 2 mi from the "D" bottle, in addition to applying a volume of 1.0 ml intramuscularly in the deltoid region of the compound "B" and, if necessary, 3 ml more of the cell regeneration compound, using a volume of 1 ml of the bottle "B", 1 my bottle "C" and 1 ml of the bottle "D" this volume is applied locally in the site that is intended to regenerate.

5. - The applications of the "Compound of Cellular Regeneration" (CRC) in other diseases in which currently there is no real option, which allows to induce cell regeneration (neurogenesis, angiogenesis, vasculogenesis, chondrogenesis, osteogenesis and myogenesis) that may be of utility in the treatment of incurable diseases, as a support that allows to improve the general conditions of the patient and their quality of life, as an external source of replacement of diseased cells and tissues.